Metabolomics and serum pharmacochemistry revealed the preventive mechanism of Gushudan in kidney‐yang‐deficiency‐syndrome rats

Abstract

Kidney-yang-deficiency-syndrome (KYDS) is a metabolic disease caused by neuroendocrine disorder. Gushudan (GSD) is a traditional Chinese medicine prescription with the effect of nourishing kidney and strengthening bones. In this study, the mechanism of preventive effect of GSD on KYDS was explored by integrating metabolomics and serum pharmacochemistry. Reversed-phase/hydrophilic interaction chromatography-ultra-high-performance liquid chromatography-Quadrupole-Orbitrap high-resolution mass spectrometry (RP/HILIC-UHPLC-Q-Orbitrap HRMS)based serum metabolomics indicated metabolic disturbances of KYDS rats, and 50 potential biomarkers including L-threonine, succinic acid and phytosphingosine were obtained, which were mainly involved in alanine, aspartate and glutamate metabolism, citrate cycle (tricarboxylic acid cycle) and glycerophospholipid metabolism, among others. Serum pharmacochemistry identified 29 prototypical ingredients and 9 metabolites of GSD after administration, such as icaritin and xanthotoxol. The combination of 10 serum migration ingredients in GSD, including icaritin and osthole, with 7 important targets, including AKT serine/threonine kinase 1 (AKT1) and MAPK14, was found to be key for GSD to prevent KYDS in the network pharmacology study. This study provided a new idea for the research of pathogenesis of diseases and the pharmacodynamic mechanism of traditional Chinese medicine.

Integrated untargeted and targeted testicular metabolomics to reveal the regulated mechanism of Gushudan on the hypothalamic‐pituitary‐gonadal axis of kidney‐yang‐deficiency‐syndrome rats

“…Modern medical research has shown that KYDS is a metabolic disease associated with genetics and environment. Neuroendocrine disorders caused by dysfunction of the hypothalamic‐pituitary‐gonadal (HPG) axis are the main pathological mechanisms of KYDS (Lu et al, 2023; Pan et al, 2006). The main function of the HPG axis is to promote reproductive maturation by stimulating the gonads to produce sex hormones.…”

“…Previous studies have confirmed its prevention of KYDS. Metabolomics and serum medicinal chemistry methods have shown that 10 components of GSD, including Epimedium glycoside and Serpentine, in association with targets such as AKT1 and MAPK4, modulate signaling pathways such as PI3K‐AKT1, which is the key to the prevention of KYDS by GSD (Lu et al, 2022). Fecal metabolomics studies have revealed the role of intestinal flora imbalance in the pathogenesis of KYDS and the mechanism of GSD in preventing KYDS through the “gut‐kidney” axis (Tong et al, 2022).…”

An integrated fecal metabolomic based on 1H‐NMR and UPLC‐QTOF‐MS revealed the preventive mechanism of Gushudan on glucocorticoid‐induced osteoporotic rats

“…Therefore, the integration of detection instruments is conducive to increasing the detection range of metabolites. MS and nuclear magnetic resonance (NMR) techniques are the main analytical methods in metabolomics research (Lu et al, 2022). Among them, ultra‐high‐performance liquid chromatography‐quadrupole time‐of‐flight‐mass spectrometry (UPLC‐QTOF‐MS) has high sensitivity and high resolution.…”